ASTHMA CAUSED BY THE COMPLEX SALTS OFPLATINUM

BY

DONALD HUNTER, REGINALD MILTON and KENNETH M. A. PERRY

From the Department for Research in Industrial Medicine (Medical Research Council), The London Hospital

Platinum is a rare metal of the group which in-cludes ruthenium, rhodium, palladium, osmium andiridium. Up to 1915 almost the whole of theworld's platinum production came from alluvialdeposits in Russia and Colombia. In these depositsthe platinum occurs as native metal alloyed withsmall amounts of the other metals of the group andwith iron. In more recent years other sources ofthe platinum metals have become available. Themost important new source is the nickel-copper-ironsulphide ores of the Sudbury district of Ontario,Canada, which are worked primarily for their nickeland copper contents, but which yield in additionvery important amounts of the platinum metals.A second new source is the sulphide-bearing noriteof the Potgietersrust and Rustenburg districts of theTransvaal. In the Sudbury ores the platinum ispresent chiefly in combination with arsenic, and inthe South African ores it is combined with sulphur.New alluvial deposits have also been developed inAlaska, Abyssinia and elsewhere.

Platinum and its alloys are manufactured into sheet-and wire for use in jewellery, dentistry, and the chemicaland electrical industries. These products are madechiefly by the usual metallurgical processes of melting,casting, forging, rolling, and wire drawing. Recently,however, the increased production of finely dividedmetal powders from complex platinum salts has led toincreased handling of these salts in the precious metalindustry.Of the many and varied uses of platinum, attention is

directed here more particularly to the use of the platinumsalts and their aqueous solutions. The chemical industryhandles considerable quantities of hexachloroplatinicacid, H2PtCl6, in the manufacture of platinum catalysts.The electroplating industry deposits platinum fromaqueous solutions containing various platinum salts suchas sodium hexahydroxy-platinate Na2Pt(OH),,, dinitro-diammino platinum (Pt2NH3(NO2)2), and from phos-phate solutions.

In photography use is made of a paper sensitized witha mixtqre of potassium chloroplatinite K2PtCl4, andferric oxalate. Barium platino-cyanide BaPt(CN)4, isused in x-ray fluorescent screens. In opthalmologyDuggen and Narravala (1941) described the use ofplatinum chloride for the tattooing of opacities in thecornea. Stenius (1941) used it as a histological methodfor staining the visual purple.The literature of the toxicology and pharmacology of

platinum and its salts is scanty. The first mention ismade in 1827 when Gmelin described the effects ofplatinum chloride on animals. Prevost (1833) describedits use in the treatment of epilepsy. Hofer (1840) advo-cated the use of platinum perchloride (PtCl4) and sodium

chloroplatinite (Na2PtCl6) in the treatment of syphilisPedler (1878) showed that platinum perchloride inacti-vates cobra venom in vitro, though Brunton and Fayrer(1878) pointed out that this was due to the formation ofan insoluble compound with cobra poison and not toany action of platinum itself. The platinum perchlorideis a chemical antidote and has no power to modify orprevent the action of the venom after its absorption intothe blood. Carozzi (1934) gave an account of a chemistwho developed discomfort, weakness, vertigo, and aremarkable acceleration of respiration and pulse ratesabout two hours after watching spongy platinum meltedin refractory crucibles. White fumes which rose fromthe crucible, when heated with an oxyhydrogen flame,turned green. The platinum had been prepared fromthe residues of gold-bearing ores from Russia containingtellurium and other impurities.

Hofmeister (1882) described experiments showing thetoxic effects of platinum ammine chlorides on frogs andrabbits. He showed that they first caused an increaseof reflex sensitivity and even convulsions, and laterfibrillary twitchings and a 'curare'-like paresis of thenerve endings in muscle. In the rabbits there were alsoepileptiform seizures and loss of consciousness. Hard-man and Wright (1896) reported the death of a childaged 7 months who died five hours after the accidentaladministration of 8 gr. of potassium chloroplatinite.The child had previously been ill and a necropsy revealeda chronic ileo-colic intussusception. Chemical analysisdetected the presence of platinum in the stomach andduodenum, but it was not present in any other organ.The immediate cause of death was considered to becardiac syncope; but since the child was described asbeing in a feeble state of health, the case does not con-tribute much to present knowledge of the toxicology ofplatinum salts. The only reference to any toxic effectin adults is by Karasek and Karasek (1911) who inexamining the workers in forty photographic studios inChicago found eight cases of poisoning characterized bypronounced irritation of the throat and nasal passages,causing violent sneezing and coughing. There was alsobronchial irritation causing respiratory difficulties sogreat that some individuals were entirely unable to usethe paper containing potassium chloroplatinite Irrita-tion of the skin causing cracking, bleeding and pain, wasalso observed

Environmental Conditions in Platinum RefineriesA full account is given of the metallurgy and

methods of refining of the precious metals in theImperial Institute reports on the mineral industryof the British Empire and foreign countries (1936);and in 1937 Johnson and Atkinson recorded themethod used at the Acton refinery of the MondNickel Company (fig. 1). Whatever method is usedin refining, the platinum is precipitated in the formof one of its complex salts, either ammonium chloro-

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ASTHMA CAUSED BY THE COMPLEX SALTS OF PLATINUM

FIG. 1.-Wet-process department in Acton refinery ofthe Mond Nickel Company.

platinite (NH4)2PtCI6, which is then ignited toproduce platinum sponge, or sodium chloro-platinite Na2PtCl66H20. The platinum spongemay then be sieved preparatory to further treatment.Sometimes the complex salts are handled in dry formand sometimes in a wet process. If they get into theatmosphere in the dry process it is in the form ofdust, and in certain stages of the wet process theyare thrown into the atmosphere in the form ofdroplets in a fine spray. The process of sieving thespongy platinum causes a dust of metallic platinum.The environmental conditions have been investi-gated in four refineries. At refinery A, a wetprocess involving sodium chloroplatinate was inoperation; at refinery B a wet process caused theprecipitation of ammonium chloroplatinate whichwas then dried; at refinery C dry ammoniumchloroplatinate was handled, mostly under excellentexhaust ventilation, though where the salt wascrushed this was less good, and at refinery Dammonium chloroplatinate, after precipitation, wasignited to form spongy platinum. The wholeoperation was carried out under exhaust ventilation,there being no anxiety about loss since the preciousmetals were recovered from the exhaust by anelectro-static precipitator.

Estimation of Platinum Salts and Metal inLow Concentrations

The platinum content of the atmosphere atvarious points in these refineries was estimated. Avolume of air was sucked through a particulatefilter at a known flow-rate for a given time, usuallyduring the whole of an operation. Air-borne con-centrations of platinum dusts encountered in theprocess laboratories and factories may consist ofsoluble platinum salts, platinum metal or platinummetal mixed with other precious metals. If amixture of precious metals was present, the followingtechnique was employed.

Principle. The particulate filter with the mixtureof precious metals was digested with aqua regia andbrought into solution. Thallium nitrate was thenadded to form a thallium complex of the precious

metals; this was rendered alkaline with ammonia,when the complexes of all the metals except platinumwere dissolved and removed. The platinum com-plex was then dissolved off the paper with acid, andreduced to the platinous state by the addition ofstannous chloride. Estimation of the orange colourof the platinous chloride by the colorimetric methodof Snell and Snell (1936), gave a quantitativemeasurement of the concentration of platinum.

Technique. (i) The filter pad containing the dustsample was placed in a Kjeldahl flask and thoroughlydigested with a few millilitres ofaqua regia. The contentsofthe flask were then heated almost to dryness, care beingtaken not to char the digest. 20-30 ml. of water wereadded, together with a few drops of a 1 per cent. solutionof thallium nitrate. After the formation of the thalliumcomplex was complete, the solution was renderedalkaline with ammonium hydroxide and filtered. Thefilter paper was thoroughly washed with ammonia toremove all traces of the salts of extraneous metals.

(ii) The filter containing the platinum-thallium com-plex was then subjected to a further aqua regia digestionand carefully heated almost to dryness as before. A fewmillilitres of concentrated hydrochloric acid were addedand the solution was boiled again to remove all tracesof nitric acid. If necessary a second boiling withhydrochloric acid was carried out. To remove thehydrochloric acid the solution was evaporated to drynessand redissolved in water, and twice again evaporatedto dryness.

(iii) The sample was then dissolved in a knownvolume of 3-3 per cent., -by volume, solution of hydro-chloric acid in distilled water and filtered. If this solu-tion showed any yellow colour from the nitration of thefilter paper, this colour was measured by the HilgerSpekker photo-electric colorimeter, and the readingsubtracted from the reading obtained, later, after thedevelopment of the platinum colour. To 10 ml. ofthis solution (or an aliquot diluted to 10 ml. with thehydrochloric acid solution) was added 0 1 ml. of 40 percent. stannous chloride (SnCl2) in concentrated hydro-chloric acid. The presence of platinum was shown bythe development of a yellow-orange colour, which after15 minutes development time was related to the amountof platinum in solution within a range of 10-500,ug (,ug is1/1000 mg.). If greater sensitivity was required, thesolution after filtering was heated to dryness, and thendissolved in 5 ml. of the solution. In this way themethod was made twice as sensitive as that alreadydescribed. Even greater sensitivity may be obtainedby dissolving the salt in 2-0 ml. of hydrochloric acidand taking readings on a sensitive photo-electric colori-meter with a mirror galvanometer. This micro-readingtechnique will give estimations as low as 0 5,ug of platinumin solution. It is, however, so delicate that it is difficultto apply in the presence of large amounts of residuefrom filter paper digestion.

Calibration Curves. (Figs. 2 and 3.)(a) Using Spekker colorimeter, with 10-ml. cup and

dark blue filters.

jig Pt.02050100150

Spk. reading0S

112534

(b) Using micro-photometerviolet figures.

,ug Pt.0*00*51-01-5

Galvanometerdifference

0*03.5659-2

,ug Pt. Spk. reading200 48250 58300 67400 82500 94with 2-ml. cups and

jug Pt.2-02-5303.5

Galvanometerdifference

11-2133014-615 8

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BRITISH JOURNAL OF INDUSTRIAL MEDICINECalibration Curve using Spekker Colorimeter with

10-ml. Cup and Dark Blue Filters.

Platinum ,ug.FIG. 2.

Calibration Curve using Micro-Photometer with2-ml. Cups and Violet Filters.

Platinum ,ug.FIG. 3.

When the sample consisted only of soluble platinumsalts the filter pad was digested with concentrated hydro-chloric acid. The solution so obtained was diluted andfiltered. It was then evaporated to dryness twice, afterbeing dissolved in water, to remove excess hydrochloricacid. The platinum was then estimated by the colori-meter technique described in paragraph (iii) above.When the sample contained metallic platinum, but no

other precious metals, it was not necessary to carry outthe process described in paragraph (i), but the estimationwas made according to the technique described inparagraphs (ii) and (iii).

A. 1. Neutralizing platinum salts.. .. 18 pg/m32. ,,5 20

3. Separating crystals of platinum salts 7

. 936. Sieving spongy platinum metal ..400

B. 1. Aqua regia treatment of crude plati-num metals concentrate .. .. 2-0 ug/m3

2. Precipitation and filtration of impure(NH4)2PtCl6 .. .. .. 3-4

3. Dissolving impure platinum spongein aqua regia .. .. .. 3-6

4. Precipitation and filtration of pure(NH4)2PtCI6 .. .. .. 1-6

5. Discharging dry (NH4)2PtCl6 from)drying ovens .. .. .. I

6. Hand crushing and packing dry >50-2(NH4)2PtCl6 and (Pd2NH3Cl2) inashless filter paper.

7. Precipitation and filtration of impure(Pt2NH3Cl2) .. .. .. 2-0

8. Purification of rhodium .. .. 6-99. Recovery of small amounts of pre-

cious metals from solutions byzinc reduction .. .. .. 3il

10. Discharging residues from dryingovens .. .. .. .. 4-1 ,,

C. 1. Crushing ammonium chloroplatinate 1700 ptg/m32. Atmosphere near reducing fumace .. 63. Aqua regia attack on platinum .. 1 54. Sieving spongy platinum .. .. 960

D. 1. Aqua regia attack on platinum metal l 0 ,g/m32. ,, ,, ,, ,,1 0.9 ,,93. Atmosphere near reducing bath fur-

nace .. .. .. .. .. 3-2 ,,4. General atmosphere of P.M. dept... 2-0

In refinery B, estimations were also made by spectro-graphic methods described by Fothergill, Withers andClements (1945), and similar figures were obtained atthe same sampling points.

Investigation of WorkersAll the workers in these four refineries were inter-

viewed. The history of any illness involving nasalor chest symptoms was obtained. Their occupa-tional history was taken, and any family history ofasthma was noted. They were examined clinically,and 15 in. x 12 in. radiographs were taken of theirchests. Full blood counts were obtained from allof them. An attempt was made at refinery A totest their skin sensitivity by injecting intradermally2 minims of a 1/10,000 solution of sodium chloro-platinate. Unfortunately nearly half the workersrefused this test, apparently owing to a fear ofbecoming sensitive to the salt. In the rest the intra-dermal test was unsatisfactory; and at refinery B apatch test had been previously tried and had givenequivocal results. Skin tests were therefore notpersisted with in refineries B, C and D.The age and sex of the employees in the four

refineries were as follows:

Re-finery 29and 30-39 40-49 50-59 Over TotalReiey under 60 Toa

A male .. 5 4 4 6 1 20female.. - 3 1 4

B male .. 10 19 30 13 2 74C male .. 3 2 2 1 - 8

female 1 - - - 1D male .. 1 2 2 2 7

Total .. 20 30 39 22 3 114

They had worked in platinum refineries for thefollowing number of years

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ASTHMA CAUSED BY THE COMPLEX SALTS OF PLATINUM

Re- 4and 5-9 10-14 15-19 20-24 25and Totalfinery under over

A 6 4 1 3 4 6 24B 12 13 7 13 18 11 74C 8 1 - - - - 9D 1 2 1 - 2 1 7

Total 27 20 9 16 24 18 114

Many of the men in these refineries suffered froma syndrome similar to that described by the Karaseksin Chicago in 1911. It started with repeatedsneezing and was followed by profuse running ofthe nose with a watery mucous discharge. Thenfollowed tightness of the chest, shortness of breath,cyanosis and a wheeze. These symptoms wouldpersist so long as the men were in the factory andfor about one hour after they left. The symptomswould then subside,'but often the man would wakein the early hours of the morning with a bout ofcoughing which might last half an hour. A com-pensatory polycythaemia was observed in one manseen during an attack. Some men also complainedof a scaly erythematous dermatitis, and some of anurticarial rash. The following case histories aregiven as examples of the syndrome.

Case 1. R. C., aet. 58, research chemist, worked inrefinery A from 1907 to 1924 (18 years). From thefirst year at this work he noticed a tightness of the chestwith a wheeze when certain processes in the refinerywhich caused a spray were in operation. He noticed atightening also in the muscles of the back and markedsneezing. There was a watering of the eyes and a dis-like of light. He would go home and go straight tobed, and would wake up in the morning quite fit, onlyto repeat the same symptoms the next day. He wasforced to leave the refinery in 1924 because the symptomsbecame so bad he could no longer carry on. Since thenhe has been perfectly well. On one occasion he returnedto the refinery on business and immediately noticed atightness of his chest, even though the process to whichhe was sensitive was not going on in the room. How-ever, it was discovered that sodium chloroplatinate hadbeen weighed out in the room about half an hour pre-viously. There was no family history of asthma. Henow showed no abnormal physical signs. His bloodcount was 4,160,000 red cells per c.c., haemoglobin111 per cent. (photo-electric estimation of alkalinehaematin 100 per cent., equivalent to 13-8 gm. haemo-globin per cent.), white cells 12,200, polymorphs 61 percent., small lymphocytes 6 per cent., large lymphocytes27 per cent., large hyalines 6 per cent. Dr. D. Jenningsreported on an x-ray of his chest-old bilateral apicalinfection with fibrosis and drawing upward of bothhila; emphysema of both bases.

Case 2. A. W., male, aet. 38, started work at the ageof 15 in a chocolate manufacturing factory. He workedhere for 6 months and then transferred to platinumrefinery A. After six years on this work he noticed thatwhen certain processes were in operation his nosestarted to run and he would start sneezing. This lastedfor half an hour. The symptoms gradually got worseand after ten years he began to get tightness of hischest, shortness of breath, wheeze and cough, but heproduced no sputum. He never had an attack at home.The attacks gradually got more frequent and moresevere, and two months before he was interviewed hewas moved to the ' other precious metals ' department.Since this move he has not had a further attack. Hehad had no previous illness, and there was no family

history of asthma. On examination no abnormalphysical signs were found, except that when he painteda 3 per cent. solution of sodium chloroplatinate on hisforearm a large wheal appeared. His blood countshowed 5,120,000 red cells, 100 per cent. haemoglobin(photo-electric estimation), 11,200 white cells, 50 percent. polymorphs, 41 per cent. lymphocytes, 3-5 percent. eosinophils, 5-5 per cent monocytes. X-rays ofhis chest showed emphysema.

Case 3. E. V. N., chest, assistant manager of wetprocess at refinery B, aet. 28, had worked for five yearsin the laboratory and for 24 years as assistant managerof the wet process. Immediately he started on theprocess he became aware that if he entered the roomwhere ammonium chloroplatinate was dried his nosestarted to run, producing perfectly clear fluid. Hewould soak three handkerchiefs in an hour. He woulddevelop severe sneezing attacks and some irritation ofhis eyes. After he had been there three months thesesymptoms were followed by tightness of the chest whichwould last for half an hour, and wheezing which lasted5 hours. He would be awakened in the early hours ofthe morning with a cough which might last an hour, butthe following day he would be quite fit. He had hadno previous illness, and there was no family history ofasthma. He entered the drying-room on the day hewas interviewed and was observed in an attack. Hewas cyanosed, dyspnoeic and had an audible wheeze.His respiration rate was 34. He had no clubbing of hisfingers. His chest moved evenly, was hyper-resonantwith normal air entry but many sibilant rhonchi through-out. There were no other abnormal physical signs.His blood count showed 6,350,000 red cells, 130 per cent.haemoglobin (photo-electric estimation), 8200 whitecells, 60 per cent. polymorphs, 30 per cent. lymphocytes,5 per cent. eosinophils, 1 per cent. basophils and 4 percent. monocvtes. X-ray of his chest revealed no ab-normality. During the attack he was given 10 minimsof 1/1000 adrenalin intramuscularly, but it did notproduce any relief of the symptoms, though it raisedthe pulse rate from 80 to 120.

Case 4 L. J., aet. 36, process hand, worked 7 yearsat a chemical plant and then for 14 years at platinumrefinery B on the wet process and in the ' other preciousmetals' department. During the past 3 years he hadhad attacks of running nose, sneezing, shortness ofbreath, tightness of the chest, wheeze and cough. Hewas frequently awakened by attacks of coughing at2 a.m., and had had such an attack every night for thethree months previous to his sick-leave which hadlasted 3 weeks at the time of interview. He had neverhad any attacks while away from the works. He wasmoved to the time office, but still got some attacks, andwas therefore transferred to another department wherehe would not be exposed to the salts of platinum. Hehad had pleurisy at the age of 8, and had his tonsilsremoved 1 year previously because of his asthma. Therewas no family history of asthma. When examined hehad not been at the refinery for three weeks, so heappeared a healthy man, and showed no abnormalphysical signs. His blood count showed 4,760,000 redcells, 104 per cent. haemoglobin (photo-electric estima-tion), 7450 white cells, 57 per cent. polymorphs, 1 5 percent. eosinophils, 39-5 per cent. lymphocytes and 2 percent. monocytes. Dr. M. H. Jupe reported on an x-rayof his chest as follows:-'There are a few scatteredcalcified nodules over the lung fields. The hilar shadowsare well seen, but not excessive.'

Case 5. M. D., female, aet. 20, had worked as apress operator before entering platinum refinery C;3 months before her interview she was observed sievingspongy platinum without exhaust ventilation or mask,and was seen to be without any symptoms. She saidthat when she handled the dry complex salt her eyes andnose would run, and she sneezed continuously. Sheexperienced some tightness of the chest the same evening,but this never woke her at night. She had never beenill, and had no family history of asthma. On examina-

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BRITISH JOURNAL OF INDUSTRIAL MEDICINE

tion she had no abnormal physical signs. Her bloodcount showed 4,500,000 red cells, 98 per cent. haemo-globin (photo-electric estimaton), 12,000 white cells,58 per cent. polymorphs, 2 per cent. eosinophils, 34 percent. lymphocytes, 6 per cent. monocytes. X-ray of herchest revealed no abnormality.

Case 6. A. A., chemist, aet 33, for past 4 years hadbeen in charge of platinum refinery D. For 12 yearsbefore that he had been an analytical chemist. He hadno symptoms except when he treated the filtrates withgranulated zinc; this caused effervescence and dropletscontaining complex salts to be thrown into the atmo-sphere Then his nose ran and he sneezed. This mightlast for half an hour. He had no tightness of his chest,shortness of breath, cough or wheeze. He had hadscarlet fever as a child, but there was no family historyof asthma. On examination, apart from a very milddegree of funnel chest, he had no abnormal physicalsigns. His blood count showed 5,950,000 red cells,118 per cent. haemoglobin (photo-electric estimation),7000 white cells, 60 per cent. polymorphs, 36 per cent.lymphocytes, 1 per cent. eosinophils, and 3 per cent.monocytes.

Analysis of the occupation of the workers whocomplained of these symptoms and of the circum-stances in which they occurred, produced con-clusive evidence that the complex salts of platinumare the cause of the syndrome. The sieving ofspongy platinum produces a much higher concen-tration of platinum in the atmosphere than theprocesses involving the complex salts. Workershave been observed sitting over this process withoutexhaust ventilation and without wearing masks; yetin no instance has asthma been found to ariseamong workers while engaged on this sieving. Intwo instances in refinery A and in three instancesin refinery B, workers who complained of asthmawere removed from the platinum refining depart-ment to the ' other precious metals ' department,where they handled principally ruthenium and

rhodium without recurrence of the symptoms.The incidence was highest in those in contactwith the complex salts in their dry form, butdid occur also in those engaged on certain partsof the wet processes where droplets of the com-

plex salts were thrown into the atmosphere.Maintenance men and men engaged on packing thecomplex salts stressed the fact that the dust imme-diately produced the symptoms described. Inrefinery C the symptoms were most severe wherethe salt was crushed, and at this point the complexsalt concentration in the atmosphere was exception-ally high. It was interesting that the authorities atrefineries A, B and C were well aware that thesyndrome had been occurring in their refineries formany years, yet those at refinery D had never heardof it. On investigation the explanation was evident.At refinery D the ammonium complex salt was pre-cipitated under exhaust ventilation, and thenignited to form spongy platinum, again with exhaustventilation. Loss of the precious metal was notconsidered since it was trapped from the exhaustand recovered by an electro-static precipitator.There was thus no dust and no spray. There was,however, in this refinery, a process in which thefiltrates were treated with granulated zinc, andthere was a fine spray and no exhaust ventilation.The men were only in contact with the process fora few minutes at a time, and while none complainedof shortness of breath, tightness of the chest or

wheeze, 5 out of 7 said they noticed sneezing andrunning of the nose of short duration.

Analysis of occupation and symptoms showedthat out of 91 men in contact with the complexsalts of platinum, 52 have the asthmatic syndrometo some degree. The following table (Table 1).

TABLE 1

Number showingX-ray of chest eosinophilia above

Number.Nun__er300 per c.c.

Refinery Number Occupation Number Number Number Notemployed in refinery with wditih Number with Handling Ndoitasthmadrmatitis with calcified Hadlinge hadlingeemphysema costal doule sdoublecartilage salts salts

A 24 Manager .. 1 0Ceramic Dept. 1 1* - 1* 1 *Bullion Dept. I 1* 1* 1 -Wet process.. 18 6 3 1 - 2Maintenance 1 1O.P.M. .. 2 2* 2* 1* -

B 74 Manager .. 3 3 1 1 2Wet process.. 29 14 3 3 5 7 6Ignition and

drying-rooms 4 3 1 2Packing salt.. 2 2 1 1Maintenance 10 4 - 1 1Laboratory .. 12 1 t - - 5Furnace 6 - 4-O.P.M. .. 8 3* 3* 1 2 4

C 9 Dry process .. 9 6 2 3D 7 All processes 7 St - _

Total .. 114 Number in con-tact with com-plex salts ofplatinum .. 91 52 13 11 6 24 19

* Developed syndrome on wet process and moved to another department with complete relief.t Handles complex salts of platinum.t Mild symptoms of running nose and sneezing when on process producing spray.

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ASTHMA CAUSED BY THE COMPLEX SALTS OF PLATINUM 97

gives the data of this analysis, as well as information FREQUENCY DISTRIBUW CURVE OFon radiographic evidence of emphysema and calci- 15 HAEMOGLOBIN /IN P.A7IJN^f REF/IERrfication of the costal cartilages, and the numbers ofworkers with a total eosinophil count in the bloodabove 300 per c.c.Of the men examined, 13 had suffered from skin /

lesions: these were mostly of a scaly erythematous i itype, though some were urticarial. They were con- ifined to the parts of the body exposed either to dustQAor spray, involving principally the hands and fore-arms, but in the more severe cases the face and neckwere also involved. The condition was not materi-ally different from that which might be found in anychemical factory and diagnosed under the generalheading, 'industrial dermatitis.' One of the workers o AAat refinery A was so sensitive that on painting a 5s 6- 10 10 /20 /303 per cent. solution of sodium chloroplatinate on FII o5his arm a well marked wheal appeared within twominutes. Skin tests, which were carried out in FREQUENCY DIS7WRJMOUN CURVE OFrefinery A by injecting intradermally 2 minims of a WHITE CELl5 IN RA77NJVH REflAiERS1/10,000 solution of sodium chloroplatinate, gavelittle information. The results are shown in Table 2. -v

FREQUENCY D0STRIBlITI CURVE Of h-30 AED CELLS IN PLATINUM REFINERS

257

E2 .3 .4 (3 14898/X/iw2 / | 710TAL WHIrE CELLS /I 77IOUANDS PER ML.

FIG. 6.

Examination of the x-ray films of the chest of

this group of workers revealed nothing outstanding.It would be expected that emphysema would developin those who had repeated attacks of asthma, and

the incidence of radiological signs of emphysemaand catarrhal bronchitis is high. Another observa-

o tion was that in 6 instances there was gross calcifi-

3S 4.0 4-S 5-0 SS 60 6-5- cation of the costal cartilages. This incidence isRED CELLS MIL/LION/S PER Mr L. probably higher than would be found in a similar

FIG. 4. group of the population at large. Evidence of

TABLE 2

Skin test resultsCase No. Sex Age Symptoms

Immediate 24 hours 48 hours

1036 M 38 Asthma 3-mm. wheal Nil Nil1037 M 29 Nil Nil I$ ,,1038 M 64 ,, 5-mm. wheal. ,, ,1039 M 54 ,, Nil1042 M 31 Running of nose1043 M 35 Asthma ,, 2-5-mm. wheal1044 M 56 ,, ,, 3-mm. wheal1045 M 45 Dermatitis 15-mm. wheal Nil1050 M 51 Nil Nil 6-mm. wheal 6-mm. wheal1051 M 49 Asthma and dermatitis Nil Nil1052 M 56 Asthma ,, ,1053 M 55 ,, ,, 4-mm. wheal1054 M 43 ,, ,, 3-mm. wheal1055 F 48 ,, ,, 4-mm. wheal1056 F 33 5-mm. wheal Nil1058 F 39 Nil Nil

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BRITISH JOURNAL OF INDUSTRIAL MEDICINEFREQUENCY (%STRIBRION CURVE OfPOLYMORPHS IN PLATIN/UM( REFINERS

S /0 7e 0 r ~~ r-~

/4

LI%

10

Y ''1'4

o 2-5 3-0 3-5 4-0-f5 o_io-5 6.0 iS 70 15 &O Sqo0--§./0TOTAL POLYMOtIPHS IN ThW&4DS PER ML.

FIG. 7.

r,REQUE,4CY DISTRIBUTIOA CURVE OFE05NOPH/LS /IN PLATINUM REfIANERS

/57

/0

5

50%Z. tCV tICJ v%W LJr^4-,A nL %.W 'nA C^'I"x.w A r' An 'V,% i

s a50W zW I -160..s4s 4su .5L ax,} OwcDCOW XPTrOAL EOSINOPNIILS AUMDREDS PER H L.

FIG. 8.

arrested or calcified pulmonary tuberculosis wasfound in 5 instances, and active disease was presentin one instance.The blood counts revealed normal red cell counts

and haemoglobin levels, except for case 3 who wasobserved in an attack, and had a marked com-pensatory polycythaemia. There is, however, atendency towards a polymorphonuclear leuco-cytosis, but this is probably of no significance sincethe range of variation in white cell counts in theindustrial population during the war has been wide.The eosinophil counts tend to be high, but noneare extremely high. Frequency distribution curveshave been drawn from all these figures.

Prevention and TreatmentPrevention of this syndrome can be achieved by

not allowing the complex salts of platinum to reachthe atmosphere of the workshop, either in the formof dust or spray. This can be achieved by exhaustventilation. Dust is worse than spray; therefore,

unless it is necessary for technical reasons, it isadvisable that the double salts of platinum shouldnot be dried. Masks give some protection, butsince they introduce the human factor, they areunsatisfactory.Treatment consists of removal from exposure to

the dust or spray. It is advisable to wash awaythe salts from the nose with water. Fresh airrelieves the symptoms more quickly than anythingelse. Oxygen may help to relieve symptoms; andAdrenalin injected intramuscularly may help torelieve a severe attack.

SummaryA syndrome consisting ofrunning of the nose, sneezing,

tightness of the chest, shortness of breath, cyanosis,wheezing and cough is described.

This syndrome occurred in 52 out of 91 men exposedto the dust or spray of the complex salts of platinum.

Thirteen men complained of dermatitis.These syndromes did not arise in men exposed to

much higher concentrations of metallic platinum in theatmosphere, or to men exposed to the complex salts ofthe other precious metals, including palladium.

Prevention is by exhaust ventilation.

AcknowledgmentsWe should like to express our gratitude to the precious

metal refining companies and their managers for theircourtesy in allowing us to carry out this investigation,and for their help during it.We are indebted to Dr. James Maxwell, Mr. A.

Parker Hague and Dr. A. J. Amor for drawing ourattention to the existence of the condition, to Dr. M. H.Jupe and Dr. D. Jennings for reporting on the radio-graphs, to Mr. H. J. Ferrier for taking them, and toMr. W. D. Duffield and Mr. L. Hoskins for technicalhelp.

REFERENCESBrunton, T. L., and Fayrer, J. (1878). Proc. roy. Soc., 27, 465.Carozzi, L. (1934). Occupation and Health, Geneva, 2, 669.Duggan, J. N., and Narravala, B. P. (1941). Brit. J. Ophthal., 20, 419.Fothergill, S. J. R., Withers, D. F. W., and Clements, F. S. (1945).

Brit. J. industr. Med., 2, 99.Gm6lin, C. G. (1827). Edinb. J. med. Sci., 3, 324.Hardman, R. S., and Wright, C. H. (1896). Brit. med. J., 1, 529.Hofer, F. (1840). J. Pharm. Chem., 27, 213.Hofmeister, F. (1882). Arch. exper. Path., 16, 393.Imperial Institute, Mineral Resources Dept. Reports on the Mineral

Industry of British Empire and Foreign Countries (1936).Platinum and Allied Metals.

Johnson, C., and Atkinson, R. H. (1937). Trans. Instit. chem. Eng.,15, 131.

Karasek, S. R., and Karasek, M. (1911). Rep. Ill. State CommissionOcc. Dis., p. 97.

Pedler, A. (1878). Proc. roy. Soc., 27, 17.Prevost, J. L. (1833). Ann. Chem., 5, 231.Snell, F. D., and Snell, C. T. (1936). Colorimetric Methods of

Analysis, New York, 1, 418.Stenius, S. (1941). Acta phys. scand., 1, 380.

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